There has been a paradigm shift in the dogma that the heart becomes terminally differentiated shortly after the neonatal period. This dogma has been overturned with the widely accepted discoveries of not only dividing cardiomyocytes but also resident stem cells contained within myocardial niches. (Anversa et al., 1998; Kajstura et al., 1998, Beltrami et al., 2001). It has been determined that this pool of stem cells is not made up of mobilized bone marrow cells, but are actual stem cells residing within the myocardial tissue itself (Beltrami et al., 2003). However, noting the plethora of varying phenotypes present within the myocardium that contribute to both functional and structural integrity of the organ, it is unlikely that the populations of c-kit-positive cardiac stem cells disclosed in Anversa et al., 1998; Kajstura et al., 1998; and Beltrami et al., 2001 are solely responsible for not only maintenance of homeostasis but also mounting response to myocardial injury.
Various isolation methods have been described to obtain cardiac stem cells (CSCs; see e.g., Hierlihy et al., 2002, Bearzi et al., 2007; Goumans et al., 2007; Smith et al., 2007). Several reports describe that CSCs can be isolated after explant and/or enzymatic dissociation based on expansion centered on the expression of membrane antigens such as c-kit and Sca-1 (see e.g., Bearzi et al., 2007; Goumans et al., 2007, Laugwitz et al., 2005). Most of these isolation methods are based on antigen-antibody interactions and magnetic bead sorting. To date, this is the best option for synthesis of a clinical grade therapeutic product as the single use of reagents limits introduction of pathogens unlike other purification techniques such as fluorescence based sorting by use of enzymatic activity or fluorophore coupled antibody to target interaction, although other cell sorting systems such as the Sony Cell Sorter SH800 that employs a disposable plastic chip can also be used for clinical applications.